PROJECT SUMMARY/ABSTRACT The proposed project aims to address a current gap in our understanding of the role of biological sex in overall survival among melanoma AJCC TNM stages IIA/IIB/IIC/IIIA/IIIB/IIIC/IIID. We will evaluate methylome alterations and mutational burden in the primary tumors of 1000 melanoma patients with the goal of 1) identifying underlying mechanisms for observed disparities in melanoma overall survival between men and women, and 2) identifying subclasses of methylome alterations and mutational signatures associated with sex and survival.